page_title: Discovery and development of statins
section_title: Differences in statin structure
hierarchical_section_title: Discovery and development of statins / Statin drug design / Differences in statin structure
caption_attribution_description: English: Fluvastatin
context_page_description: The discovery of HMG-CoA reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused by it.
context_section_description: The statins differ with respect to their ring structure and substituents. These differences in structure affect the pharmacological properties of the statins, such as:
  Affinity for the active site of the HMGR
  Rates of entry into hepatic and non-hepatic tissues
  Availability in the systemic circulation for uptake into non-hepatic tissues
  Routes and modes of metabolic transformation and elimination
  Statins have sometimes been grouped into two groups of statins according to their structure.
  Type 1 statins
  Statins that have substituted decalin-ring structure that resemble the first statin ever discovered, mevastatin have often been classified as type 1 statins due to their structural relationship. Statins that belong to this group are:
  Lovastatin (Figure 2)
  Pravastatin
  Simvastatin
  Type 2 statins 
  Statins that are fully synthetic and have larger groups linked to the HMG-like moiety are often referred to as type 2 statins. One of the main differences between the type 1 and type 2 statins is the replacement of the butyryl group of type 1 statins by the fluorophenyl group of type 2 statins. This group is responsible for additional polar interactions that causes tighter binding to the HMGR enzyme. Statins that belong to this group are:
  Fluvastatin (Figure 3)
  Cerivastatin
  Atorvastatin
  Rosuvastatin
  Lovastatin is derived from a fungus source and simvastatin and pravastatin are chemical modifications of lovastatin and as a result do not differ much in structure from lovastatin. All three are partially reduced napthylene ring structures. Simvastatin and lovastatin are inactive lactones which must be metabolized to their active hydroxy-acid forms in order to inhibit HMGR. Type 2 statins all exist in their active hydroxy-acid forms. Fluvastatin has indole ring structure, while atorvastatin and rosuvastatin have pyrrole and pyrimidine based ring structure respectively. The lipophilic cerivastatin has a pyridine-based ring structure.
caption: Fig.3 Fluvastatin, a type 2 statin
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